College of Dentistry & College of Medicine, The Ohio State University, Columbus, Ohio 43210, USA
Address for correspondence: Firdaus S. Dhabhar, 4179 Postle Hall, College of Dentistry & College of Medicine, The Ohio State University, 305 W. 12th Ave., Columbus OH 43210. Tel: 614-688-8562; fax: 614-247-6945.
dhabhar.1{at}osu.edu
Ann. N.Y. Acad. Sci. 992: 205-217 (2003).
Delayed type hypersensitivity (DTH) reactions represent cell-mediated
immune responses that exert important immunoprotective (resistance
to viruses, bacteria, and fungi) or immunopathologic (allergic
or autoimmune hypersensitivity) effects. We have used the skin
DTH response as an
in vivo model to study neuro-endocrine-immune
interactions. We hypothesized that just as an acute stress response
prepares the cardiovascular and musculoskeletal systems for
fight or flight, it may also prepare the immune system for challenges
(e.g., wounding) that may be imposed by a stressor (e.g., an
aggressor). Studies showed that acute (2 hours) stress experienced
before primary or secondary cutaneous antigen exposure induces
significantly enhanced skin DTH. This enhancement involves innate
as well as adaptive immune mechanisms. Adrenalectomy eliminates
the stress-induced enhancement of DTH. Acute administration
of physiological concentrations of corticosterone and/or epinephrine
to adrenalectomized animals enhances skin DTH. Compared with
those in controls, DTH sites from acutely stressed or hormone-injected
animals show significantly greater erythema and induration,
numbers of infiltrating leukocytes, and levels of cytokine gene
expression. In contrast to acute stress, chronic stress is immunosuppressive.
Chronic exposure to corticosterone or acute exposure to dexamethasone
significantly suppresses skin DTH. These results suggest that
during acute stress, endogenous stress hormones enhance skin
immunity by increasing leukocyte trafficking and cytokine gene
expression at the site of antigen entry. Elucidation of mechanisms
mediating a stress-induced enhancement of skin immune function
is important because such immunoenhancement can have protective
(wound healing, resistance to infection) or pathological (allergic
or autoimmune hypersensitivity) consequences.
